Regulatory Open Forum

I am going through the RAPS course materials for Intermediate Medical Writing. The lesson on the CTD details sections in a "marketing application." The next lesson details sections of the "New Drug Application," which are the same, and which the course refers to as the "marketing application" within the module. Is there a difference? Also, when submitting an NDA, does the sponsor have to have pivotal Phase 3 study results? The course indicates that it does but I thought that you could submit an NDA before launching Phase 3 trials? 

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Elizabeth Earley
El Cajon CA
United States
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Hi Elizabeth.

First for the simple answer - you "marketing application" and "NDA" are identical and for the same purpose - to get FDA approval of your product to be launched onto the market with approved claims language, dosage, administration routes, etc.  So there is no difference - just potentially a difference between what 2 people call the documents and maybe some update "carry-over" issues for the online course.

As for your question of Phase III - I have never seen an application approved WITHOUT phase III data.  These are the multi-center statistically significant studies FDA usually needs to get the safety and efficacy information in randomized controlled large scale studies required by Keufhauer (I KNOW I misspelled that!) amendments. With that said, FDA OFTEN will require "post-market" or "post-approval" or "Phase IV" studies of the drug in a larger population of users to further craft and update safety and warning information and which have sometimes led to things like black box warnings.

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Victor Mencarelli
Sr. Manager - Regulatory Affairs
Hain Celestial Group
United States

Original Message:
Sent: 26-Aug-2016 15:27
From: Elizabeth Earley
Subject: Difference between marketing application and NDA

I am going through the RAPS course materials for Intermediate Medical Writing. The lesson on the CTD details sections in a "marketing application." The next lesson details sections of the "New Drug Application," which are the same, and which the course refers to as the "marketing application" within the module. Is there a difference? Also, when submitting an NDA, does the sponsor have to have pivotal Phase 3 study results? The course indicates that it does but I thought that you could submit an NDA before launching Phase 3 trials? 

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Elizabeth Earley
El Cajon CA
United States
------------------------------

Original Message------

I am going through the RAPS course materials for Intermediate Medical Writing. The lesson on the CTD details sections in a "marketing application." The next lesson details sections of the "New Drug Application," which are the same, and which the course refers to as the "marketing application" within the module. Is there a difference? Also, when submitting an NDA, does the sponsor have to have pivotal Phase 3 study results? The course indicates that it does but I thought that you could submit an NDA before launching Phase 3 trials? 

------------------------------
Elizabeth Earley
El Cajon CA
United States
------------------------------

Original Message------

I am going through the RAPS course materials for Intermediate Medical Writing. The lesson on the CTD details sections in a "marketing application." The next lesson details sections of the "New Drug Application," which are the same, and which the course refers to as the "marketing application" within the module. Is there a difference? Also, when submitting an NDA, does the sponsor have to have pivotal Phase 3 study results? The course indicates that it does but I thought that you could submit an NDA before launching Phase 3 trials? 

------------------------------
Elizabeth Earley
El Cajon CA
United States
------------------------------

Just another 2 cents into the mix - nomenclature in regulatory is often confusing.  As others have noted, "marketing application" is a universal term for many different types of specific submissions (NDA or BLA in the US, NDS in Canada, etc.) intended to request approval for commercial use.  Even amongst countries that all use the CTD, there are obvious differences (i.e., Module 1) and more subtle differences, such as the amount and type of data required in Module 3.  Your course may be giving general guidance on the CTD, and specifically giving additional information on the requirements for a US NDA.

Next - the "Phase" of a study is determined in large part by how the data is intended to be used.  In standard, conservative development, you are absolutely right that there would be Phase 1 (initial safety), Phase 2 (initial proof of concept), and Phase 3 (supporting marketing application) studies.  But in real life, there are Phase 1/2, Phase 2/3, Phase 1b, Phase 2b, Phase 2b/3, etc. studies.  You're unlikely to see studies labeled Phase1/3, because the intent of these studies are very different - the data you get from Phase 1 would be very unlikely to support marketing.  There are always exceptions, however, particularly for serious or life-threatening indications with unmet medical need, especially if the indication is in an orphan population where it is difficult to conduct clinical studies.  If you do receive marketing approval based on what would ordinarily be Phase 2 data, expect extensive post-marketing confirmatory studies.

Hope this helps!

Cathy

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Catherine Anderson PHD
Senior Manager - Regulatory CMC
Hillsborough NC
United States

Original Message:
Sent: 29-Aug-2016 12:54
From: David Lim
Subject: Difference between marketing application and NDA

Liz,

Victor and Tom provided valuable information.

There can be an exception depending upon regulatory pathways.

Under the FDA's accelerated program, Merck's Keytruda, the first anti-PD-1 (humanized mAb), was approved based on phase Ib trial results. It was indicated for advanced melanoma. 

Thank you.

s/ David

______________________________________________

Dr. David Lim, Ph.D., RAC, ASQ-CQA 

Regulatory Doctor and Compliance Seminars 

http://www.regulatorydoctor.US

Phone (Toll-Free): 1-(800) 321-8567

E-mail:  David@RegulatoryDoctor.US

Schedule an appointment here 

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"Knowledge is power only when it is practiced and put into action." - Regulatory Doctor

NOTICE: This communication (including any attachments) may contain privileged or confidential information intended for a specific individual and purpose, and is protected by law. If you are not the intended recipient, you should delete this communication and/or shred the materials and any attachments and are hereby notified that any disclosure, copying or distribution of this communication, or the taking of any action based on it, is strictly prohibited.

Thanks, everybody! Very helpful information.

I have some follow up questions:  

1. There is such a thing as a pre-marketing application, yes? This isn't an NDA or a BLA and it doesn't have Phase 3 data. Is it something that needs to be formally submitted and approved via CDER/CBER? Or is it strictly an informal head's up to the agency that and NDA/BLA is forthcoming?

2. Also, is there a place for IBs and study protocols in the application? If so, where? 

3. Finally, what's the deal with clinical trial applications? Are they submitted in CTD format? What content do they include beyond study protocol and design?

Thank you in advance!

------------------------------
Elizabeth Earley
El Cajon CA
United States

Original Message:
Sent: 29-Aug-2016 14:14
From: Catherine Anderson
Subject: Difference between marketing application and NDA

Just another 2 cents into the mix - nomenclature in regulatory is often confusing.  As others have noted, "marketing application" is a universal term for many different types of specific submissions (NDA or BLA in the US, NDS in Canada, etc.) intended to request approval for commercial use.  Even amongst countries that all use the CTD, there are obvious differences (i.e., Module 1) and more subtle differences, such as the amount and type of data required in Module 3.  Your course may be giving general guidance on the CTD, and specifically giving additional information on the requirements for a US NDA.

Next - the "Phase" of a study is determined in large part by how the data is intended to be used.  In standard, conservative development, you are absolutely right that there would be Phase 1 (initial safety), Phase 2 (initial proof of concept), and Phase 3 (supporting marketing application) studies.  But in real life, there are Phase 1/2, Phase 2/3, Phase 1b, Phase 2b, Phase 2b/3, etc. studies.  You're unlikely to see studies labeled Phase1/3, because the intent of these studies are very different - the data you get from Phase 1 would be very unlikely to support marketing.  There are always exceptions, however, particularly for serious or life-threatening indications with unmet medical need, especially if the indication is in an orphan population where it is difficult to conduct clinical studies.  If you do receive marketing approval based on what would ordinarily be Phase 2 data, expect extensive post-marketing confirmatory studies.

Hope this helps!

Cathy

------------------------------
Catherine Anderson PHD
Senior Manager - Regulatory CMC
Hillsborough NC
United States

Original Message:
Sent: 29-Aug-2016 12:54
From: David Lim
Subject: Difference between marketing application and NDA

Liz,

Victor and Tom provided valuable information.

There can be an exception depending upon regulatory pathways.

Under the FDA's accelerated program, Merck's Keytruda, the first anti-PD-1 (humanized mAb), was approved based on phase Ib trial results. It was indicated for advanced melanoma. 

Thank you.

s/ David

______________________________________________

Dr. David Lim, Ph.D., RAC, ASQ-CQA 

Regulatory Doctor and Compliance Seminars 

http://www.regulatorydoctor.US

Phone (Toll-Free): 1-(800) 321-8567

E-mail:  David@RegulatoryDoctor.US

Schedule an appointment here 

FDA Guidance LinkedIn Google Plus Twitter Facebook Tumblr

"Knowledge is power only when it is practiced and put into action." - Regulatory Doctor

NOTICE: This communication (including any attachments) may contain privileged or confidential information intended for a specific individual and purpose, and is protected by law. If you are not the intended recipient, you should delete this communication and/or shred the materials and any attachments and are hereby notified that any disclosure, copying or distribution of this communication, or the taking of any action based on it, is strictly prohibited.